Tumor necrosis factor--alpha gene promoter polymorphisms in Chinese patients with nonalcoholic fatty liver diseases

Nonalcoholic Fatty Liver Disease (NAFLD) encompasses a histopathological spectrum of clinical conditions such as simple fatty liver (steatosis), nonalcoholic steatohepatitis (NASH), and a variant that has degrees of fibrosis. Tumor Necrosis Factor-alpha (TNF-alphalpha) is considered essential for NAFLD. Therefore, we investigated the correlation between TNF-alphalpha gene promoter polymorphism and NAFLD in this human study.

The TNF-alpha gene polymorphisms at position -238 and -308 were analyzed in 189 Chinese patients with NAFLD and 138 healthy controls by using polymerase chain reaction and restriction fragment length polymorphism assay. The serum levels of TNF-alpha in both patient and control groups were measured by ELISA. The associations of TNF-alpha polymorphism and serum TNF-alpha, and/or insulin resistance, and/or clinical features were analyzed.

The carrier frequencies of TNF-alpha gene polymorphism with G/A mutation at -238 were significantly higher in the patients with NAFLD than those in the control subjects (p < 0.05). However, there were no significant differences between the NAFLD patients and control subjects in the polymorphisms at -308 (p > 0.05). In addition, the serum level of TNF-alpha was markedly higher in the patients with NAFLD than in the control subjects (p < 0.05). There were significant associations between TNF-alpha gene polymorphism in the -238 A allele and increased serum TNF-alpha, insulin resistance, as well as increased body mass index in the NAFLD patients.

The results indicate that the TNF-alpha gene polymorphism at position -238 is associated with susceptibility of nonalcoholic Fatty Liver Disease in a Chinese population.